Overexpression Of C17orf59 Induces Autophagy In Glioma Cell Lines By Eliminating The Rag Bridge Between Ragulator And Mtorc1

Objecct: Malignant glioma is a high incidence of primary intracranial tumor,clinical comparison,accounts for the highest proportion of intracranial tumors,the incidence rate ranked first,and its incidence is increasing year by year,mainly due to influence of environment,gene and other adverse factors.In recent years,a large number of scholars,medical researchers,around the disease to explore and in-depth study and found that 88% of patients with glioblastoma multiforme generally within the next 3 years died of the disease.Therefore,the clinical workers put the treatment of glioma in an extremely important position,at present in the treatment of the disease is the main choice of surgical treatment,and postoperative radiotherapy and chemotherapy.Because of the blood-brain barrier(BBB),the main factors of the blood brain barrier is glioma,blood brain barrier can enter blocking immune cell invasion and chemotherapy of small molecules,which is a special structure to limit the diffusion of tumor chemotherapy,BBB limited molecular weight more than 180 U water soluble substances through,but most of the water soluble drug and its molecular weight is between 200-1200 U.Thus,even with combination chemotherapy and antibody therapy,the disease has not been cured successfully.As a kind of solid tumor,malignant tumor is the main cause of the disease.As the glioma was invasive growth,so surgery is difficult to cut,postoperative recurrence rate,mortality are relatively high.In the occurrence and development of human solid tumors,the excessive division and proliferation of tumor cells become the most significant feature.At the same time associated with cell division essential protein replication system activation,a large number of protein production,the division of cells to provide the necessary material basis,therefore,a large number of intracellular protein synthesis of tumor cells to become an indispensable condition.Malignant glioma is one of the most malignant tumors of human history,excessive division of the proliferation of the formation of a large number of immature glial cells is a significant pathological features of malignant glioma.MTORC1 is a protein complex that controls autophagy,ribosome biogenesis and mRNA translation.Rag acts as a bridge between the Ragulator complex and the mTORC1 complex,allowing mTORC1 to be raised to the surface of lysosomes and activated by Rag GTP in the presence of amino acids or insulin.With the deepening of research,gene therapy has been proved to be the main treatment for this disease.In order to find a new target gene that is helpful to the treatment of glioma,we further elucidate the molecular mechanism of splenic proliferation and invasion of human glioblastoma,and provide theoretical basis for its diagnosis and treatment.Methods: We collected seven human glioma cell lines for further study.To study the expression of these genes in human glioma cell lines,the autophagy of several cells,the relationship between the expression of this gene and the autophagy flux,and the down-regulation of the gene,the effect of mTORC1 influences.In addition,an MTT assay was performed to measure the effect of the gene overexpression on cell viability.Results: we collected 7 human glioma cell lines for further study.We found that c17orf59 gene was highly expressed in M059K cells,but had low expression in U-87 GM cells.The difference of gene expression is related to many factors,among which the most important factor is cell signal transduction pathway.In this study,we also found that M059K cells possessed higher U-87 GM cells with less autophagic flux.In addition,the relationship between c17orf59 expression and autophagy flux was also studied.And for the first time,we found that up regulation of c17orf59 gene expression could induce autophagy in human glioma cells by disrupting the interaction of mTORC1-Rag-Ragulator.MTT assay was performed to measure the cell viability of c17orf59 and M059K cells in the U-87 GM and c17orf59 cells,and the cell death was significantly increased after over expression.Thus,these data suggest that c17orf59 may provide a valuable therapeutic strategy for the treatment of malignant gliomas.Conclusions: 1.There is a correlation between the expression of c17orf59 and the autophagy flux in the glioma cell line.O overexpression of c17orf59 in glioma cell lines can induce autophagy,but deletion does not affect autophagy 3.overexpression of c17orf59 disrupts Rag-Ragulation interactions and inhibits mTORC1 activity in U-87 GM and M059K cells.4.Overexpression of c17orf59 Induces evidence of autophagy-related cell death in human glioma cells.The deletion of c17orf59 did not alter mTORC1 activity in human glioma cell lines U-87 GM and M059K cells.